1. Field of the Invention
The present invention relates to the synthesis of a chromium amino acid nicotinate complex which has glucose tolerance factor activity.
2. Description of the Related Art
In addition to being part of several enzyme systems, chromium is associated with a low-molecular weight organic complex termed glucose tolerance factor (GTF) that acts with insulin in promoting normal glucose utilization. Brewer's yeast, which is rich in GTF, has been shown to improve glucose tolerance, lower serum cholesterol and triglycerides in some elderly subjects, and to reduce insulin requirements in some diabetics. Glucose tolerance is usually impaired in protein-calorie malnutrition and some cases have shown a dramatic response to trivalent chromium.
Purified extract from Brewer's yeast containing chromium, nicotinic acid, glycine, glutamic acid and cystine has been shown to have GTF activity (Toepfer, et al, "Chromium Foods in Relation to Biological Activity", J. Agric. Food Chem, Vol 21, p. 69, 1973). A synthesis procedure to prepare complexes with a similar composition having GTF activity also has been reported (Toepfer, et al, "Preparation of Chromium-Containing Material of Glucose Tolerance Factor Activity from Brewer's Yeast Extracts and by Synthesis", J. Agric Food Chem., Vol 25, p. 162, 1977).
In this synthesis procedure, chromium complexes were prepared by dissolving 4 grams of Cr(Ac).sub.3 H.sub.2 O in 750 milliliters of 80% alcohol containing 2 milliliters of glacial acetic acid that was neutralized with NH.sub.4 OH to pH 7. Four (4) grams of nicotinic acid (molar equivalent 2:1 Cr) was added to the contents of the flask and was stirred during refluxing for 3 hours until a distinct color change occurred. Successively, 2.4 grams of glycine (2:1 Cr), 2.4 grams of L-glutamic acid (1:1 Cr), and 2.5 grams of L-cysteine-HCl (1:1 Cr) were added during 4 hours of continuous stirring and refluxing. The material was stirred overnight without being heated. Alcohol was removed in vacuo, the solution was filtered to remove suspended insoluble material, the residue was washed with water, and filtrate and washings were combined and reduced in vacuo to 300 milliliters. This solution of crude material was a deep red color at pH 4.3. This solution was then subjected to purification (see Toepfer, et al (1977) at p. 163).